Kimmtrak®

The first T cell receptor (TCR) therapy, Kimmtrak® (tebentafusp-tebn – Immunocore), was approved by the U.S. Food and Drug Administration (FDA) on Jan. 25, 2022. It also is the first drug indicated to treat adults who have uveal melanoma that is positive for HLA-A*02:01 and that cannot be removed by surgery or that has metastasized. The uvea is the colored parts of the eyes. Consisting of a T cell receptor bound to an anti-CD3 immune-effector, Kimmtrak is a bispecific T cell engager that attaches to a peptide presented by HLA-A*02:01 antigens, which are prevalent on melanoma cells, causing them to disintegrate. It will be administered by intravenous (IV) infusions at 68mcg once every week following two smaller loading doses. Its label has a boxed warning that some patients may experience cytokine release syndrome (CRS), a potentially severe acute inflammatory reaction from using Kimmtrak. With a U.S launch expected within the next few weeks, cost and distribution information is not yet available. Full prescribing information is here.

At a Glance

• Brand (Generic) Name: Kimmtrak (tebentafusp-tebn)
• Manufacturer: Immunocore
• Date Approved: Jan. 25, 2022
• Indication: for the treatment of adult patients who have unresectable or metastatic uveal melanoma that is HLA-A*02:01-positive
• Dosage Forms Available: single-dose vials containing 100mcg of Kimmtrak in 0.5mL of solution for reconstitution and IV infusion
• Launch Date: within weeks
• Estimated Annual Cost: Not yet available
• Uveal melanoma is a rare and aggressive form of cancer, which occurs in the internal layers of the eyes. It affects an estimated five persons per million in the United States. Metastases, which occur for about one-half of patients, decrease projected survival rates to approximately one year.
• Diagnosed mostly in patients over 60 years old, uveal melanoma is slightly more common for men than women and much more prevalent for individuals who have light-colored eyes.
• Kimmtrak sticks to a protein expressed by uveal melanoma tumors. It also stimulates T cells to produce cytokines and other proteins that directly attack tumor cells.
• A phase III clinical trial included 378 previously untreated patients who were confirmed to have metastatic uveal melanoma and an HLA-A*02:01 genotype. Patients received therapy with either Kimmtrak or one of three other drugs currently used off label to treat uveal melanoma. After 12 months, 27% of patients receiving Kimmtrak had died versus 61% of those receiving other treatment. Overall survival (OS) was 21.7 months for those in the Kimmtrak group compared to 16.0 months for the others.
• Patients should be watched for at least 16 hours after the first few infusions for signs of CRS, which could include fever, headache, low blood pressure, rash and vomiting. Patients receiving Kimmtrak also may have increased blood levels of creatinine, glucose and/or liver enzymes, but levels of hemoglobin and/or lymphocytes may be decreased.
• Kimmtrak is the first drug specifically indicated for treating uveal melanoma. Current treatment mainly is off-label use of an immunotherapy, such as Keytruda® (pembrolizumab), or the chemotherapy drug, dacarbazine.
• Kimmtrak was approved as a Breakthrough Therapy as well as under the FDA’s Real-Time Oncology Review (RTOR) program.

Ryaltris Approved

Glenmark Specialty received approval from the U.S. Food and Drug Administration (FDA) on Jan. 13, 2022, for Ryaltris™ (olopatadine/mometasone) Nasal Spray. Indicated for patients who are at least 12 years old, it combines a histamine blocker and a corticosteroid to treat seasonal allergic rhinitis symptoms. Its recommended dose is two sprays in each nostril two times a day for a total daily dose of eight sprays. In two clinical studies that included more than 2,300 patients, those using Ryaltris had better relief from both nasal and ophthalmic allergy symptoms than participants who used either of its components separately, or who used a placebo spray. Mild side effects, which included changes in taste, nose bleeds and irritation in the nose, were experienced by fewer than 5% of patients. Glenmark’s partner, Hikma Specialty U.S.A., will be the supplier for the U.S. The launch date and pricing are not yet available.

Expanded Indication for Rinvoq

Approximately one month after the FDA granted an additional approval to Rinvoq® (upadacitinib – AbbVie) extended-release tablets for treating certain adults who have psoriatic arthritis (PsA), the agency also approved Rinvoq for the treatment of atopic dermatitis. On Jan. 14, 2022, Rinvoq was approved for patients who are 12 years old and older, who weigh at least 40kg (88 pounds) and who have not had adequate results from prior treatment, including with a biological drug. The recommended dose is 15mg once daily, which can be increased to 30mg/day if needed, but only for patients under the age of 65 years. Rinvoq should not be taken at the same time as biologic disease-modifying anti-rheumatic drugs (DMARDs), immunosuppressants or other JAK inhibitors are being used. It includes the same boxed warning required by the FDA for all JAK inhibitors that are used to treat inflammatory conditions. Patients taking them may have a greater chance of dying, developing certain cancers, suffering cardiovascular (CV) events, having blood clots and acquiring severe infections. Patients also should be screened for tuberculosis (TB) before starting treatment with a JAK inhibitor and periodically while therapy continues. Rinvoq originally was FDA approved in August 2019 for the treatment of adults who have moderately to severely active rheumatoid arthritis (RA) that is not managed with methotrexate, or who cannot tolerate methotrexate treatment. Here is Rinvoq’s updated prescribing information.

Two Zydelig Indications Withdrawn

Gilead Sciences is withdrawing two indications, which were granted conditionally in 2014, for Zydelig® (idelalisib) tablets. Because they were awarded under the FDA’s Accelerated Approval process, the indications for treating recurrent cases of follicular B-cell non-Hodgkin lymphoma (FL) or small lymphocytic leukemia (SLL) needed to be confirmed by additional clinical trial results. However, a number of new drugs for the two indications have been approved in the last few years. Partly due to the availability of effective new treatment options, Gilead has had trouble recruiting participants for clinical studies. Therefore, it has decided not to continue seeking full approvals. It will confer with healthcare professionals to help move patients being treated with Zydelig for FL or SLL to other therapies. Zydelig also has a fully approved FDA indication for use in combination with rituximab to treat relapsed chronic lymphocytic leukemia (CLL), which remains active. The labeling for Zydelig contains a boxed warning and it has a risk evaluation ad mitigation strategy (REMS) about increased risks of serious liver damage, diarrhea, colitis, pneumonitis, infections or intestinal perforation, that have been associated with its use. Updated prescribing information will be here.

Cibinqo® (abrocitinib)

Pfizer received approval from the U.S. Food and Drug Administration (FDA) on Jan. 14, 2022, for Cibinqo® (abrocitinib). It is a Janus-associated kinase (JAK) inhibitor that will be used for the treatment of moderate-to-severe atopic dermatitis for adult patients who have not had relief from or who cannot use other systemic drugs, including biologics. The recommended dose is 100mg once a day, which can be adjusted to 200mg if the patient is not responding, or to 50mg for patients who have kidney failure. A boxed warning that is required for all JAK inhibitor labeling describes their potential to cause blood clots, cancer, cardiovascular (CV) events or serious infections, including tuberculosis (TB). For the first three months of therapy, Cibinqo should not be used at the same time as an antiplatelet drug. Pfizer plans a launch in the coming weeks, but pricing and distribution details are not yet known. Here is prescribing information.

At a Glance

• Brand (Generic) Name: Cibinqo (abrocitinib)
• Manufacturer: Pfizer
• Date Approved: Jan. 14, 2021
• Indication: for the treatment of adults who have refractory, moderate-to-severe atopic dermatitis and whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable
• Dosage Forms Available: 50mg, 100mg and 200mg tablets
• Launch Date: in the coming weeks
• Estimated Annual Cost: Pricing information is not yet available.
• Atopic dermatitis is a common form of eczema, a group of chronic skin diseases that involve inflammation and cause itchy, irritated bumps, crusts and scales on the skin. It usually begins in childhood, with most patients having a first episode before the age of five years. Symptoms may improve and worsen unpredictably. Inflammation and scratching eventually can thicken and toughen the skin.
• According to the Asthma and Allergy Foundation of America, around 7.3% of American adults (about 18 million people) have atopic dermatitis. Moderate-to-severe forms of the condition are estimated to affect approximately two of every five patients aged 18 years or older.
• Cibinqo helps to decrease inflammation by blocking the actions of an enzyme that relays inflammatory signals inside cells.
• In three separate clinical trials, patients taking Cibinqo for 12 weeks had significantly better scores than participants given placebo tablets on the primary measures of atopic dermatitis severity – the Investigator Global Assessment (IGA), the Eczema Area and Severity Index (EASI) and the Peak Pruritus Numerical Ratings Scale (PP-NRS).
• In the studies, 5% or more of Cibinqo-treated patients experienced headaches, nausea or nasal or throat infections.
• A boxed warning outlines the increased risks of blood clots, cancers, serious infections and death that may be associated with the use of any JAK inhibitor. Patients taking one of them also should be screened for tuberculosis (TB) before starting treatment and periodically while therapy continues.
• Initial therapy for atopic dermatitis usually is a topical corticosteroid, with higher potency products used to treat more severe forms of the condition. A calcineurin inhibitor, such as Elidel® (pimecrolimus) cream may be used for patients who cannot use a corticosteroid or whose atopic dermatitis has not been cleared by topical corticosteroid treatment.
• Also on Jan. 14, 2022, another JAK inhibitor, Rinvoq® (upadacitinib – AbbVie) received an additional indication for treating patients at least 12 years old who have moderate-to-severe atopic dermatitis.
• Dupixent® (dupilumab – Sanofi/Regeneron) injection, which is FDA approved for treating patients as young as six years old, is an interleukin-4 alpha receptor (IL-4Rα) blocker. Adbry™ (tralokinumab-ldrm – LEO Pharma) injection, an interleukin-13 (IL-13) inhibitor, was FDA approved in December 2021. Both are indicated to treat moderate-to-severe atopic dermatitis that is not responding to topical therapy.